The present invention relates to bone graft substitute compositions and implants for new bone formation and arthrodesis. In specific applications of the invention the compositions include biocompatible calcium phosphate ceramics in synergistic combination with osteogenic compositions.
Many techniques have been developed for correcting bone defects and voids. In one approach, the void is filled with a bone paste or bone compound. In other techniques, the void is filled with a corraline substance. In these approaches, one goal is to induce the formation of new bone from the patient""s existing bone to fill the void or repair the defect.
Aspects of these techniques have also been borrowed for application in other orthopedic procedures, such as spinal fusion. Spinal fusion is indicated to provide stabilization of the spinal column for painful spinal motion and disorders such as structural deformity, traumatic instability, degenerative instability, and post-resection iatrogenic instability. Fusion, or arthrodesis, is achieved by the formation of an osseous bridge between adjacent motion segments. This can be accomplished within the disc space, anteriorly between contiguous vertebral bodies or posteriorly between consecutive transverse processes, laminae or other posterior aspects of the vertebrae.
An osseous bridge, or fusion mass, is biologically produced by the body upon skeletal injury. This normal bone healing response is used by surgeons to induce fusion across abnormal spinal segments by recreating spinal injury conditions along the fusion site and then allowing the bone to heal. A successful fusion requires the presence of osteogenic or osteopotential cells, adequate blood supply, sufficient inflammatory response, and appropriate preparation of local bone. This biological environment is typically provided in a surgical setting by decortication, or removal of the outer, cortical bone to expose the vascular, cancellous bone, and the deposition of an adequate quantity of high quality graft material.
A fusion or arthrodesis procedure is often performed to treat an anomaly involving an intervertebral disc. Intervertebral discs, located between the endplates of adjacent vertebrae, stabilize the spine, distribute forces between vertebrae and cushion vertebral bodies. A normal intervertebral disc includes a semi-gelatinous component, the nucleus pulposus, which is surrounded and confined by an outer, fibrous ring called the annulus fibrosis. In a healthy, undamaged spine, the annulus fibrosis prevents the nucleus pulposus from protruding outside the disc space.
Spinal discs may be displaced or damaged due to trauma, disease or aging. Disruption of the annulus fibrosis allows the nucleus pulposus to protrude into the vertebral canal, a condition commonly referred to as a herniated or ruptured disc. The extruded nucleus pulposus may press on the spinal nerve, which may result in nerve damage, pain, numbness, muscle weakness and-paralysis. Intervertebral discs may also deteriorate due to the normal aging process or disease. As a disc dehydrates and hardens, the disc space height will be reduced leading to instability of the spine, decreased mobility and pain.
Sometimes the only relief from the symptoms of these conditions is a discectomy, or surgical removal of a portion or all of an intervertebral disc followed by fusion of the adjacent vertebrae. The removal of the damaged or unhealthy disc will allow the disc space to collapse. Collapse of the disc space can cause instability of the spine, abnormal joint mechanics, premature development of arthritis or nerve damage, in addition to severe pain. Pain relief via discectomy and arthrodesis requires preservation of the disc space and eventual fusion of the affected motion segments.
Bone grafts are often used to fill the intervertebral space to prevent disc space collapse and promote fusion of the adjacent vertebrae across the disc space. In early techniques, bone material was simply disposed between the adjacent vertebrae, typically at the posterior aspect of the vertebrae, and the spinal column was stabilized by way of a plate or rod spanning the affected vertebrae. Once fusion occurred, the hardware used to maintain the stability of the segment became superfluous and was a permanent foreign body. Moreover, the surgical procedures necessary to implant a rod or plate to stabilize the level during fusion were frequently lengthy and involved.
It was therefore determined that a more optimal solution to the stabilization of an excised disc space is to fuse the vertebrae between their respective end plates, preferably without the need for anterior or posterior plating. There have been an extensive number of attempts to develop an acceptable intra-discal implant that could be used to replace a damaged disc and maintain the stability of the disc interspace between the adjacent vertebrae, at least until complete arthrodesis is achieved. To be successful, the implant must provide temporary support and allow bone ingrowth. Success of the discectomy and fusion procedure requires the development of a contiguous growth of bone to create a solid mass because the implant may not withstand the cyclic compressive spinal loads for the life of the patient.
Many attempts to restore the intervertebral disc space after removal of the disc have relied on metal devices. U.S. Pat. No. 4,878,915 to Brantigan teaches a solid metal plug. U.S. Pat. Nos. 5,044,104; 5,026,373 and 4,961,740 to Ray; 5,015,247 to Michelson and U.S. Pat. No. 4,820,305 to Harms at al., U.S. Pat. No. 5,147,402 to Bohler at al. and 5,192,327 to Brantigan teach hollow metal cage structures. Unfortunately, due to the stiffness of the material, some metal implants may stress shield the bone graft, increasing the time required for fusion to occur. Subsidence, or sinking of the device into bone, is also a concern when metal implants are implanted between vertebrae. Metal devices are also foreign bodies which can never be fully incorporated into the fusion mass. Moreover, fusion rates can be slower with metal implants as compared to graft.
Various bone grafts and bone graft substitutes have also been used to promote osteogenesis and to avoid the disadvantages of metal implants. Autograft is often preferred because it is osteoinductive. Both allograft and autograft are biological materials which are replaced over time with the patient""s own bone, via the process of creeping substitution. Over time a bone graft virtually disappears unlike a metal implant which persists long after its useful life. Unfortunately, the use of autograft presents several disadvantages. Autograft is available in only limited quantities. The additional surgery also increases the risk of infection and blood loss and may reduce structural integrity at the donor site. Furthermore, some patients complain that the graft harvesting surgery causes more short-term and long-term pain than the fusion surgery.
Allograft material, which is obtained from donors of the same species, is more readily obtained. However, allograft is also disadvantageous because of the risk of disease transmission and immune reactions as well as religious objections. Furthermore, allogenic bone has limited osteoinductive potential compared to autogenous bone and therefore may provide only temporary support. The slow rate of fusion using allografted bone can lead to collapse of the disc space before fusion is accomplished.
Both allograft and autograft present additional difficulties. Graft alone may not provide the stability required to withstand spinal loads. Internal fixation can address this problem but presents its own disadvantages such as the need for more complex surgery as well as the disadvantages of metal fixation devices. Also, the surgeon is often required to repeatedly trim the graft material to obtain the correct size to fill and stabilize the disc space. This trial and error approach increases the length of time required for surgery. Furthermore, the graft material usually has a smooth surface which may not provide a good friction fit between the adjacent vertebrae. Slippage of the graft may cause neural and vascular injury, as well as collapse of the disc space. Even where slippage does not occur, micromotion at the graft/fusion-site interface may disrupt the healing process that is required for fusion.
Due to the need for safer bone graft materials, bone graft substitutes, such as bioceramics, have recently received considerable attention. The challenge has been to develop a bone graft substitute which avoids the disadvantages of metal implants and bone grafts while capturing the advantages of both. Calcium phosphate ceramics are biocompatible and do not present the infectious or immunological concerns of allograft materials. Ceramics may be prepared in any quantity which is a great advantage over autograft bone graft material. Furthermore, bioceramics are osteoconductive, stimulating osteogenesis in bony sites. Bioceramics provide a porous matrix which further encourages new bone growth. Unfortunately, ceramic implants typically lack the strength to support high spinal loads and therefore require separate fixation before the fusion.
Of the calcium phosphate ceramics, hydroxyapatite (HA) and tricalcium phosphate (TCP) ceramics have been most commonly used for bone grafting. Hydroxyapatite is chemically similar to inorganic bone substance and biocompatible with bone. However, it is slowly degraded. xcex2-tricalcium phosphate is rapidly degraded in vivo and is too weak to provide support under the cyclic loads of the spine until fusion occurs. Developing an implant having the biomechanical properties of metal and the biological properties of bone without the disadvantages of either has been extremely difficult or impossible.
In any application involving the formation of new bone, the orthopedic surgeon is concerned first that the new bone formation be complete, and second that the creation of the new bone occur as rapidly as possible. In the case of spinal fusion, another concern is that the spinal segments be adequately supported and stabilized until arthrodesis occurs. Orthopedics practitioners have long sought compositions and implants that provide optimum performance to address these and other critical concerns.
Thus far, a need remains for a bone graft substitute composition that provides this optimum performance and that can have wide applicability in the treatment of orthopedic conditions. In the field of spinal fusion, a need has remained for fusion devices and methods which stimulate bone ingrowth and avoid the disadvantages of metal implants yet provide sufficient strength to support the vertebral column until the adjacent vertebrae are fused.
In accordance with the invention, bone graft substitute compositions are provided for new bone formation and spinal arthrodesis. The compositions include a carrier for controlled delivery of bone growth inductive factors, such as bone morphogenetic proteins. In one aspect of the invention, the carriers include a biphasic calcium phosphate ceramic having between about 2-40% hydroxyapatite and about 98-60% tricalcium phosphate by volume and preferably a calcium/phosphorous ratio of between about 1.50 to about 1.60.
In other embodiments, the carriers preferably include a biphasic calcium phosphate ceramic having between about 5-20% hydroxyapatite and about 95-80% tricalcium phosphate by volume and most preferably about 20% hydroxyapatite and about 80% tricalcium phosphate.
The invention also contemplates osteoinductive compositions including the carriers and an effective amount of a bone growth inductive factor, such as substantially pure bone morphogenetic protein, dispersed within the ceramic. The composition preferably has a weight ratio of factor to ceramic of no more than about 1:200. In specific embodiments, the weight ratio of factor to ceramic is between about 1:200 and about 1:2000.
Spinal implants are also provided which include a body having a wall sized for engagement within a space between adjacent vertebrae to maintain the space and a confining matrix for confining new bone growth to the matrix. The matrix includes a biphasic calcium phosphate ceramic which degrades at a rate to provide calcium and phosphate for the new bone growth without reduced density of adjacent host bone and an effective amount of a substantially pure osteogenic factor bound to the ceramic.
One object of the present invention is to provide a bone graft substitute composition that provides a stable matrix for rapid growth of new bone into a space, such as a bone defect, void or fusion site. A more specific object of this invention is to provide spinal implants and compositions for arthrodesis of a motion segment which exploit all of the advantages of ceramic implants while avoiding the corresponding disadvantages. Another object of the invention is to provide a spinal implant which restores the intervertebral disc space and supports a vertebral column while promoting bone ingrowth.
One benefit of this invention is that it provides a synergistic composition of a bioceramic and an osteoinductive factor. The ceramic provides a stable scaffold for bone ingrowth and through-growth while the osteoinductive factor induces bone growth to speed the fusion rate. The increased speed of fusion allows the use of a bioceramic without the need for metal cages or internal fixation.
The ceramic also advantageously provides a source of calcium and phosphate to the fusion site. Another advantage is that the ceramic provides a matrix for confining induced bone growth to the fusion site to avoid bone growth in inappropriate locations. Other objects and further benefits of the present invention will become apparent to persons of ordinary skill in the art from the following written description and accompanying figures.